Mechanical stability of multidomain proteins and novel mechanical clamps.

We estimate the size of mechanostability for 318 multidomain proteins which are single-chain and contain up to 1021 amino acids. We predict existence of novel types of mechanical clamps in which interdomain contacts play an essential role. Mechanical clamps are structural regions which are the primary source of a protein's resistance to pulling. Among these clamps there is one that opposes tensile stress due to two domains swinging apart. This movement strains and then ruptures the contacts that hold the two domains together. Another clamp also involves tensile stress but it originates from an immobilization of a structural region by a surrounding knot-loop (without involving any disulfide bonds). Still another mechanism involves shear between helical regions belonging to two domains. We also consider the amyloid-prone cystatin C which provides an example of a two-chain 3D domain-swapped protein. We predict that this protein should withstand remarkably large stress, perhaps of order 800 pN, when inducing a shearing strain. The survey is generated through molecular dynamics simulations performed within a structure-based coarse grained model.